Complexes of DNA and specific antibody are believed to lead to tissue injury in the disease Systemic Lupus Erythematosus (SLE). Studies in our laboratory taken along with the results of other researchers suggest that the kinetics of formation and dissociation, the conformation and molecular weight of the DNA, the ratio of specific antibody to DNA, and the relative avidity of the anti-DNA antibodies may all help determine the ability of these complexes to initiate and to continue histological damage. We propose a model detailing a sequence of specific steps in disease pathogenesis. A key element in this model is the initiating role in tissue destruction played by immune complexes which contain ds DNA. In order to test the model, we will: (1) extend and refine our biophysical and immunological characterization of DNA-anti-DNA complexes; (2) make in vitro complexes of precise definition; and (3) determine by animal experiments which types of complexes can lead to tissue destruction in vivo.